Cigarette smoke impairs neutrophil respiratory burst activation by aldehyde-induced thiol modifications

H. Nguyen, E. Finkelstein, A. Reznick, Carroll E Cross, A. Van der Vliet

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Exposure to airborne pollutants such as tobacco smoke is associated with increased activation of inflammatory-immune processes and is thought to contribute to the incidence of respiratory tract disease. We hypothezised that cigarette smoke (CS) could synergize with activated inflammatory/immune cells to cause oxidative injury or result in the formation of unique reactive oxidants. Isolated human neutrophils were exposed to gas-phase CS, and the production of nitrating and chlorinating oxidants following neutrophil stimulation was monitored using the substrate 4-hydroxyphenylacetate (HPA). Stimulation of neutrophils in the presence of CS resulted in a reduced oxidation and chlorination of HPA, suggesting inhibition of NADPH oxidase or myeloperoxidase (MPO), the two major enzymes involved in inflammatory oxidant formation. Peroxidase assays demonstrated that neutrophil MPO activity was not significantly affected after CS-exposure, leaving the NADPH oxidase as a likely target. The inhibition of neutrophil oxidant formation was found to coincide with depletion of cellular GSH, and a similar modification of critical cysteine residues, such as those in NADPH oxidase components, might be involved in reduced respiratory burst activity. As α,β-unsaturated aldehydes such as acrolein have been implicated in thiol modifications by CS, we exposed neutrophils to acrolein prior to stimulation, and observed inhibition of NADPH oxidase activation in relation to GSH depletion. Additionally, translocation of the cytosolic components of NADPH oxidase to the membrane, a necessary requirement for enzyme activation, was inhibited. Protein adducts of acrolein (or related aldehydes) could be detected in several neutrophil proteins, including NADPH oxidase components, following neutrophil exposure to either CS or acrolein. Alterations in neutrophil function by exposure to (environmental) tobacco smoke may affect inflammatory/infectious conditions and thereby contribute to tobacco-related disease.

Original languageEnglish (US)
Pages (from-to)207-217
Number of pages11
JournalToxicology
Volume160
Issue number1-3
DOIs
StatePublished - Mar 7 2001

Fingerprint

Respiratory Burst
Sulfhydryl Compounds
Aldehydes
Smoke
Tobacco Products
NADPH Oxidase
Neutrophils
Chemical activation
Acrolein
Oxidants
Tobacco
Peroxidase
Pulmonary diseases
Respiratory Tract Diseases
Chlorination
Enzyme Activation
Enzymes
Halogenation
Environmental Exposure
Cysteine

Keywords

  • Aldehyde-induced thiol modifications
  • Cigarette smoke
  • Neutrophil respiratory burst activation

ASJC Scopus subject areas

  • Toxicology

Cite this

Cigarette smoke impairs neutrophil respiratory burst activation by aldehyde-induced thiol modifications. / Nguyen, H.; Finkelstein, E.; Reznick, A.; Cross, Carroll E; Van der Vliet, A.

In: Toxicology, Vol. 160, No. 1-3, 07.03.2001, p. 207-217.

Research output: Contribution to journalArticle

Nguyen, H. ; Finkelstein, E. ; Reznick, A. ; Cross, Carroll E ; Van der Vliet, A. / Cigarette smoke impairs neutrophil respiratory burst activation by aldehyde-induced thiol modifications. In: Toxicology. 2001 ; Vol. 160, No. 1-3. pp. 207-217.
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